[HTML][HTML] LKB1 tumor suppressor protein regulates actin filament assembly through Rho and its exchange factor Dbl independently of kinase activity
X Xu, T Omelchenko, A Hall - BMC cell biology, 2010 - Springer
X Xu, T Omelchenko, A Hall
BMC cell biology, 2010•SpringerBackground Germline mutations in LKB1 result in Peutz-Jeghers Syndrome characterized
by intestinal hamartomas and increased incidence of epithelial cancers. LKB1 encodes a
serine/threonine kinase that plays an important role in regulating energy metabolism
through the AMPK/mTOR signaling pathway. In addition, LKB1 is homologous to PAR-4, a
polarity protein first described in C. elegans, while activation of LKB1 in mammalian
epithelial cells induces the polarized assembly of actin filaments. Results To explore the …
by intestinal hamartomas and increased incidence of epithelial cancers. LKB1 encodes a
serine/threonine kinase that plays an important role in regulating energy metabolism
through the AMPK/mTOR signaling pathway. In addition, LKB1 is homologous to PAR-4, a
polarity protein first described in C. elegans, while activation of LKB1 in mammalian
epithelial cells induces the polarized assembly of actin filaments. Results To explore the …
Background
Germline mutations in LKB1 result in Peutz-Jeghers Syndrome characterized by intestinal hamartomas and increased incidence of epithelial cancers. LKB1 encodes a serine/threonine kinase that plays an important role in regulating energy metabolism through the AMPK/mTOR signaling pathway. In addition, LKB1 is homologous to PAR-4, a polarity protein first described in C. elegans, while activation of LKB1 in mammalian epithelial cells induces the polarized assembly of actin filaments.
Results
To explore the mechanism by which LKB1 interacts with the actin cytoskeleton, we introduced LKB1 into HeLa cells that lack endogenous LKB1. This results in activation of the small GTPase Rho and the assembly of linear actin filaments associated with focal adhesions. These effects on the actin cytoskeleton are attenuated by siRNA-mediated depletion of the guanine nucleotide exchange factor Dbl. Co-expression of the LKB1 with the adaptor protein STRAD induces actin filament puncta associated with phospho-ezrin.
Conclusions
This study reveals that LKB1 regulates the actin cytoskeleton through a Dbl/Rho pathway.
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